Apparatus, probe and method for a cryogenic system

ABSTRACT

An apparatus, probe and method for a cryogenic system are described. According to certain embodiments of the invention there is provided an apparatus for cryosurgery comprising: an exhaust line configured to receive cryogen from a probe; and a vacuum source configured to be in fluid communication with the exhaust line.

The present application is a continuation of co-pending United StatesSer. No. 14/439,883, filed Apr. 30, 2015, which is a US National Stageapplication under 35 U.S.C. § 371 of International Application No.PCT/GB2012/052700, filed 30 Oct. 2012, from which priority is claimed.

The present invention relates to an apparatus, probe and method for acryogenic system, specifically, though not exclusively for cryosurgeryand components and parts thereof.

Cryosurgery is the controlled destruction of unwanted tissue by theapplication of extreme cold. The extreme cold causes water in cells tofreeze and this freezing kills the cells. Cells are known to be killedafter exposure to temperatures below −20° C. It is known to usecryogenic systems in cryo-ablation and cryo-analgesia surgeries.

Cryosurgery is a well-established clinical technique for treating commonsoft tissue tumours in cancer cases involving the liver, kidney,prostate, breast and lung. Cryosurgery enables tumours, which areregarded as inoperable by other means, to be treated with excellentpostoperative morbidity. More recently, the technique has expanded intoother fields including podiatry for treating conditions such as Morton'sNeuroma and Plantar fasciitis. Cryosurgery Neuroablation is aneffective, safe, minimally invasive clinically proven procedure that canbe performed in the office setting.

Cryogenic systems for surgical applications generally use one of twodistinct mechanisms to achieve the required cooling.

At present the favoured cryo-surgery mechanism uses a Joule-Thompsondevice. These devices rely on the Joule-Thompson effect to inducecooling by expansion of a high pressure gas (e.g. N₂O) through a smallorifice. Such devices require the deployment of high pressure gas invivo. The high pressure gas is delivered to an expansion orifice withinthe probe, where the gas expands to produce the required cooling via theJoule-Thompson effect. If the gas escapes into the patient seriousdamage may be done. Clearly containment is a serious issue, gaseousmatter within the body can be seriously damaging. A jet of compressedgas at 1500 psi escaping from even a very small hole would causesignificant damage to soft tissue structures. Additionally if suchgaseous matter makes its way to the heart via the cardiovascular systemas cardiac arrest may result.

Further, these systems are very expensive for three principal reasons.Firstly, to achieve low temperatures the mixture of gases used areexpensive. Secondly, the probes used with these systems are for singleuse only, primarily because manufactures are reluctant to certify probesfor multiple uses which must contain high pressure gasses in vivo.Third, the Joule-Thompson effect provides a limited cooling capacity,that is—whilst Joule-Thompson devices may obtain low temperatures theircapacity to absorb heat is limited by the (relatively small) amount ofenergy absorbed by an expanding gas. Due to this limited coolingcapacity Joule-Thompson devices may require several probes for eachtreatment. Further, each probe may cost up to several thousand dollars.This gives a total treatment cost of tens of thousands of dollars pertreatment, in probes alone.

Liquid cryogenic devices rely on evaporation of a liquid, such as liquidnitrogen or helium, to produce cooling by boiling and/or evaporation.The capacity of liquid cryogenic systems to absorb heat is vastlysuperior to the capacity of Joule-Thompson devices to absorb heat. Thisis because the latent heat of vaporisation for most cryogenic fluidscommonly used in liquid cryogenic systems is significantly greater thanthe heat absorbed by the expanding gas(es) commonly used withinJoule-Thompson systems.

Currently, there may be a surgical perception that liquid cryogenicsystems can take too long to reach the temperatures required forcryosurgery. Prior art devices attempt to increase cooling speed bypressurising the liquid nitrogen feed (for instance to 275-415 kPanominal). However, once the surgeon has initiated the system the probecan still take several minutes to begin cooling.

When a prior art liquid cryogenic device is operated (from warm) itexhibits phasing within the feed line whilst the feed line is cooling tooperating temperatures. As the cryogenic liquid comes into contact witha warm (by which is meant above the boiling point of the cryogenicliquid) portion of the delivery line the cryogenic liquid boils and/orevaporates. When liquid nitrogen boils and/or evaporates the phasechange results in an approximately 700 fold increase in volume whichhinders the flow of liquid nitrogen through the feed line. Slugs ofliquid nitrogen and gas travel along the feed line until the line coolssufficiently to permit the continual flow of cryogenic liquid. Clearly,the compressibility of the slugs of gas between slugs of incompressibleliquid inhibits passage of the liquid. These effects result inefficiency losses, leading to an increase in the time between a surgeonor other operative starting the device and the device achieving asatisfactory operational state. The prior art devices attempt toovercome this phasing by pressurising the liquid nitrogen to encouragefaster cooling of the feed lines by the liquid nitrogen. This can leadto complication of the feed system and usually does not overcome intotal the issues described above.

The present invention is as set out in the independent claims.

It is an object of certain examples of the present invention to providean improved apparatus and method for liquid cryogenic systems. Variousexamples seek to overcome, or at least substantially reduce, thedisadvantages associated with the known liquid cryogenic systemsdiscussed above.

According to at least some examples of the invention there is providedan apparatus (101) for cryosurgery comprising: an exhaust line (111,211) configured to receive cryogen (103) from a probe (105); and asuction/vacuum source (107) of reduced, e.g. sub-atmospheric, pressureconfigured to be in fluid communication with the exhaust line (111,211).

According to at least some examples of the invention there is provided aprobe (105) for cryosurgery comprising: a dispersive medium (215)configured such that, in use, cryogen (103) delivered to the probedisperses within the probe through the dispersive medium.

According to at least some examples of the invention there is provided amethod and a means (109, 209, 211, 111, 107) for drawing cryogen (103)from a cryogen source for delivery to a probe (105) using a vacuumsource (107).

According to at least some examples of the invention there is provided amethod and a means (209, 215, 211) for dispersing, within a probe (105),cryogen (103) delivered to the probe through a dispersive medium (215).

According to a first aspect of the disclosure, there is provided liquidcryogen cryosurgery apparatus or apparatus for cryosurgery comprising asource of liquid cryogen, a delivery line for delivering liquid cryogento a probe, an exhaust line for receiving cryogen from a probe, a vacuumsource in fluid communication with the exhaust line.

This liquid cryogenic system enables more efficient cooling of the probethan that provided by the prior art, by overcoming, or at leastsubstantially reducing, phasing and its associated drawbacks.

A vacuum reservoir may be provided upstream of the vacuum source. Thevacuum reservoir may be in communication with a heat exchanger, heatingelement or other cryogen heating means.

A second aspect of the disclosure provides a liquid cryogen exhaustapparatus, comprising a vacuum source, an upstream vacuum reservoir, anda cryogen heating means upstream of the vacuum source.

Preferably and conveniently the cryogen heating means is located withinthe vacuum reservoir.

According to a third aspect of the disclosure, there is provided cryogenline for liquid cryosurgery apparatus, the line comprising a supplyconduit for the supply of liquid cryogen and a concentric insulatingline, the insulating conduit being continuously evacuable by a vacuumsource.

In one example a cryogen exhaust conduit, e.g. for the exhaust ofcryogen, is provided in the line, preferably concentrically between thesupply conduit and insulating conduit.

Thermally insulating spacers may be present in parts of the line outsidethe supply conduit, e.g. in the insulating conduit and/or in the exhaustconduit. Spacers may be fabricated from glass, ceramics, plastics orother materials resistant to damage from thermal cycling and or theconditions found under autoclave or other cleaning/sterilising regimes.

Another aspect of the disclosure comprises a flexible line for thesupply of cryogen in a cryosurgery apparatus, the line comprising anarray of articulated members of low thermal conductivity, each having apassage there through for the flow of cryogen.

A further aspect of the disclosure provides a probe for cryosurgery, forexample for liquid cryosurgery, the probe comprising a proximal end forconnection to a cryogen delivery line and a thermally conductive distalend for effecting cryosurgery, the probe comprising a cryogen supplyline and a cryogen exhaust line, the exhaust line being providedconcentrically about the supply line and along the entire lengththereof.

The probe may also comprise a concentric peripheral insulating conduit,being provided around the exhaust line and being continuously evacuable.

A further aspect of the disclosure provides a probe for cryosurgery, forexample for liquid cryosurgery, the probe comprising a proximal end forconnection to a cryogen delivery line and a thermally conductive distalend for effecting cryosurgery, the probe comprising a cryogen supplyline and an insulating conduit, the exhaust line being providedconcentrically about the supply line and being continuously evacuable.

A yet further aspect of the disclosure provides a liquid cryogencryosurgery apparatus or apparatus for cryosurgery comprising a primarysource of liquid cryogen and a secondary source of liquid cryogen, theprimary source supplying the secondary source with liquid cryogen,cryogen being deliverable from the secondary source to a probe whilstthe primary and secondary sources are in fluid communication to effectcryosurgery.

Preferably, the secondary source is filled with cryogen from the primarysource prior to commencing cryosurgery.

Preferably, a conduit between the primary and secondary sources ispermanently insulated, e.g. it comprises a conduit with a permanentvacuum jacket and/or other insulation. The conduit between the primaryand secondary sources may be less than 2 m, say less than 1.75, or 1.5,1.4, 1.3, 1.2, 1.1 or 1.0 m in length. A conduit between the secondarysource and the probe may be less than 2 m, say less than 1.75, or 1.5,1.4, 1.3, 1.2, 1.1 or 1.0 m in length.

The secondary source may comprise a thermocouple or other contentmeasuring device. Preferably the content measuring device may beoperable to automatically control the flow of cryogen from the primaryto secondary source.

A further aspect of the disclosure provides a method of supplying acryogen to a heat exchanger/probe, the method comprising providing asource of vacuum to draw cryogen from the heat exchanger/probe.Optionally, though not essential, the method may further comprisepressurising a source of cryogen to force cryogen to a heatexchanger/probe.

Still further aspects of the disclosure relate to methods of effectingcryosurgery using the apparatus described herein.

In order that the invention may be more fully understood, preferredexamples in accordance with the invention will now be described, by wayof example only, and with reference to the accompanying drawings inwhich:

FIG. 1 is a schematic view of a cryogenic system according to an exampleof the present invention:

FIG. 2 is a cross-sectional schematic view of a probe for use with anexample of the present invention;

FIG. 3 is a cross-sectional schematic view of an alternative probe foruse with an example of the present invention:

FIG. 4 is a schematic view of a tri-axial line for use with an exampleof the present invention;

FIG. 5 is a schematic view of the tri-axial line of FIG. 4 showing a cutaway section;

FIG. 6 is a cross-sectional schematic view of an alternative tri-axialline for use with an example of the present invention:

FIG. 7A is a cross-sectional schematic view of a bi-axial line for usewith an example of the present invention;

FIG. 7B is a cross-sectional schematic view of an alternative bi-axialline for use with an example of the present invention:

FIG. 8 is a cross-section schematic view of an insulated delivery linefor use an example of with the present invention:

FIG. 9 is a schematic view of an alternative cryogenic system accordingto an example of the present invention:

FIGS. 10, 10A and 10B are schematic views of an alternative probe foruse with an example of the present invention; and

FIG. 11A is a schematic view of a freezing mode of operation of anexample of the present invention; and

FIG. 11B is a schematic view of thawing mode of operation of the exampleof FIG. 11A.

Referring firstly to FIG. 1, a cryogenic system, indicated generally at101, comprises apparatus for supplying liquid cryogen 103, a probe 105,and a vacuum source 107. The apparatus for supplying liquid cryogen 103is connected to the probe 105 by means of delivery line 109. The probe105 is also connected to the vacuum source 107 by means of exhaust line111.

In various examples, the vacuum source 107, i.e. source of negativepressure compared to that of atmospheric pressure, is configured suchthat it can suck or draw the liquid cryogen to the probe 105.Advantageously, this avoids, or reduces the need to provide a pressuresource, i.e. a source of positive pressure compared to that ofatmospheric pressure, to force the liquid cryogen to the probe.

The apparatus for supplying liquid cryogen 103 may comprise a source ofliquid cryogen which is drawn to the probe 105 via the vacuum source107.

Optionally however, as shown in FIG. 1 with reference to the componentsin the dotted line, in one example the apparatus for supplying liquidcryogen 103 (which may be that as described in WO 96/30816) may comprisea means for supplying propellant gas 113, a Dewar 115, and a pipe 117which, in use, has an end beneath the surface of the liquid cryogen. Themeans for supplying a propellant gas 113 comprises a nitrogen gascylinder 119, which is connected to a manifold 121. The manifold 121 isconnected to a valve 123, the valve 123 is operable to regulate thepressure of the propellant gas. The valve 123 is connected to the Dewar115. In use, propellant gas is fed above the surface of the liquidcryogen contained within Dewar 115. The Dewar 115 is configured suchthat, in use, the pressure of the propellant gas may displace liquidcryogen along the pipe 117. The pipe 117 has, in use, one end beneaththe surface of the liquid cryogen contained within the Dewar 115 and theother end is connected to delivery line 109. The provision of such ameans for applying pressure to the liquid cryogen to force it throughthe delivery line 109 to the probe 105 is not essential. Instead, otherexamples rely on the provision of a downstream vacuum or reducedpressure source to draw up/suck the liquid cryogen to the probe 105.

A probe 105 for use with an example of the present invention is shown inmore detail in FIG. 2.

The probe 105 comprises a proximal end 201 and a distal end 203. At theproximal end 201 of probe 105 is a fitting 207 for connection to thedelivery line 109 and the exhaust line 111. The fitting 207 comprises aninlet 209 and an outlet 211. In use, the inlet 209 is connected todelivery line 109 and the outlet 211 is connected to the exhaust line111.

The inlet 209 is also connected to, that is in fluid communication with,tip 205 at the distal end 203 of the probe 105 by means of a deliverytube 212. Thus, in use, liquid cryogen may flow from the delivery line109 to the probe tip 205 at the distal end 203 of the probe 105 viainlet 209 and delivery tube 212.

The probe tip 205 is thermally conducting. It may also be impermeable orsemi-permeable to liquid cryogen. Thus, the probe tip 205 is operable asa heat exchanger. The outer surface 214 of tip 205 is of a thermallyconducting substance, for example gold (chosen for its conductivity andsterilisability). Within tip 205 is a region 215 of a dispersive mediumthrough which the cryogen is delivered/passed through for dispersal. Thedispersive medium 215 provides a plurality of nucleation sites for theliquid cryogen, to encourage nucleation, boiling and/or evaporation ofthe liquid cryogen passing therethrough to effect optimal thermaltransfer and heat exchange. The dispersive medium is thermallycoupled/in thermal communication with the outer surface 214 of the probetip 205. In use, the dispersive medium and the outer surface 214 of theprobe tip, are cooled due to liquid cryogen's boiling and/or evaporationwhen in contact with the dispersive medium 215. The dispersive mediummay be formed of a thermally conductive and porous material. Thedispersive medium may be formed of a sintered material. The sinteredmaterial may be a sintered: metal (such as at least one of: Aluminium,Copper and Bronze or other metals), ceramic, plastic or any othermaterial suitable for sintering.

Of course, other materials which provide plural, preferably tortuous,passageways for the passage of cryogen and the boiling thereof toenhance the dispersion of the cryogen throughout the dispersive medium,may be used for the dispersive medium.

The probe 105 also comprises an exhaust tube 217, which connects theprobe tip 205 to the outlet 211. Thus, the inlet 209 and outlet 211 arein fluid communication via the dispersive medium region 215 within thetip 205 at the distal end 203 of the probe 105.

A high volume of gas may be generated in the probe tip followingboiling/evaporation of the liquid cryogen. For example, liquid nitrogenhas an expansion ration of approximately 700 to 1. Advantageously, aporous, dispersive and diffusive medium enables the cryogen, havingtransformed from a liquid to a gaseous state, to pass through thedispersive medium and out through the outlet 211 and exhaust line 111.

Probe 105 also comprises insulated region 219. The insulation may beprovided by one or more of a vacuum, partial vacuum, or other means suchas a material with low thermal conductivity. In use, this region may bein contact with tissue which is not to be damaged by the extreme cold ofthe cryosurgery. The insulated region 219 may be fabricated to allowcleaning of the probe 105, e.g. by autoclaving. For example theinsulated region 219 may be removable or made from cleaning-resistantmaterials, a cleanable probe is likely to be re-usable.

In use, with the present cryogenic system 101 the probe insulatingregion 219 may be evacuated by the vacuum source 107.

The probe 105 is also connected to the vacuum source 107. The exhaustline 111 is connected to the outlet 211 of the probe 105. The exhaustline 111 is connected to a vacuum reservoir 125 and a pump 127 via valve129. The pump 127 is operable to produce a vacuum within reservoir 125.The vacuum pump 127 vents to the atmosphere, generally via a scavengingconnection to meet safety requirements. The valve 129 is operable tocontrol the vacuum supplied by the pump 127 and reservoir 125 to theexhaust line 111. In use, the exhaust line 111 supplies means forsupplying propellant gas 113 a vacuum to the probe 105 and the probe 105in turn supplies vacuum to the delivery line 109. Accordingly, theliquid cryogen can be urged/drawn/sucked through the delivery line 109to the probe tip via a lifting effect on the source of the liquidcryogen due to a vacuum “down-stream” of the probe tip, e.g. in theexhaust side of the system, rather than using a source of positivepressure “up-stream” of the probe tip, e.g. in the delivery side of thesystem. Advantageously, the use of a porous permeable dispersive medium,such as a sintered material, enables the lifting effect of the“down-stream” vacuum/suction to pass therethrough, thereby communicatingthe vacuum/suction to the liquid cryogen source via the delivery line.Thus, examples of the invention enable the use of negative pressurecompared to that of atmospheric pressure to draw up the liquid cryogento the probe tip rather than positive pressure to force the liquidcryogen to the probe tip. One can consider that examples of theinvention enable the liquid cryogen to be delivered to the probe tip bybeing “sucked” along to the probe tip by a vacuum or source of reduced(sub-atmospheric) pressure down-stream of the probe tip rather thanrelying on active pressure applied up-stream of the probe tip (as occursin previous cryogenic systems).

The apparatus for supplying liquid cryogen 103 and the vacuum source 107may be located within a common housing.

Previous cryogenic systems required a pump on a delivery side to createa positive pressure to force liquid coolant to the probe tip. Examplesof the present invention enable a pump at an exhaust side to be usedinstead to create vacuum (negative pressure) to cause the liquid coolantto be drawn to the probe tip.

Previous cryogenic systems suffered the drawback in that, on thedelivery side the pump and its associated fluid communication lines andvalves had to contend with liquid cryogen. Whereas with examples of thepresent invention, the pump and its associated fluid communication linesand valves only need handle the cryogen in its gaseous form. The gaseouscryogen is at a much higher temperature than liquid cryogen. Therefore,examples of the present invention enable the vacuum source pump, and itsassociated fluid communication lines and valves, to operate at muchhigher temperatures than prior art.

An alternative probe 300 is shown in FIG. 3. The alternative probe 300is similar to that described and shown in FIG. 2, only the differenceswill be described. The alternative probe 300 comprises at the proximalend 201 an additional port 301 within the fitting 207. The fitting 301is connected to vacuum insulated region 219. In this way, it is notnecessary to provide a probe 105 which is capable of holding a vacuumwithin region 219 for the entire lifetime of the probe 300. Vacuuminsulation for region 219 may be supplied by vacuum source 107 via port301. Because there are no sealed portions the probe 300 is capable ofcleaning, e.g. by autoclaving and is thus capable of re-use.

Shown in FIG. 4 is a tri-axial line 401 for use with an example of thecryogenic system 101. The tri-axial line 401 may be present from theconnector 131 to the probe 105 only or used elsewhere within thecryogenic system 101. The tri-axial line comprises a feed line 403, anexhaust line 405 and an insulating line 407. The feed line 403 is withinthe exhaust line 405 which, in turn, is within the insulating line 407.

The exhaust line 405 and the insulating line 407 act together to reduceundesirable condensation on the outside 409 of the tri-axial line 401and reduce evaporation losses from the supply of cryogen via the feedline 403.

In this example a vacuum, preferably from the vacuum source 107 isapplied to the insulating line 407. The vacuum may be provided via asplit or controllable flow so that a greater vacuum is applied to one orother of the exhaust 405 and insulating 407 lines.

FIG. 5, which is an alternative view of the tri-axial line 401, having acutaway section 501 for illustrative purposes only, shows that thetri-axial line 401 comprises a spacer 503. The spacer 503 is withininsulating line 407. The spacer 503 is made of an insulating material,for example glass or ceramics. The spacer 503 acts to prevent theexhaust line 405 from touching the insulating line 407. In this way theeffectiveness of the insulating line 407 is increased. Performance ismarkedly increased when the tri-axial line 401 is bent, as in thisformation the spacer 503 prevents the exhaust line 405 from touching theinsulating line 407. The spacers 503 are positioned along the length ofthe tri-axial line. They may be any shape but they must allow thepassage of fluids so as not to inhibit exhaust flow and so on.

FIG. 6 shows an alternative tri-axial line 601 in cross sectionalschematic view. The alternative tri-axial line 601 also comprises acentral delivery line 603, an exhaust line 605 and a peripheralinsulating line 607. However, the insulating line 607 does not have aseparate connector at the end of the line 601. Instead, vacuum isprovided within insulating line 607 by the vacuum supplied to exhaustline 605. This vacuum is supplied by means of valve 609, valve 609permits flow of fluids from insulating line 607 to exhaust line 605only. In this way any vacuum applied to exhaust line 605 will becomepresent in insulating line 607, however, if insulating line 607comprises a vacuum and an exhaust line 605 is pressurised relative toinsulating line 607 then the vacuum in insulating line 607 will remainsubstantially intact. The alternative tri-axial line 601 also featuresinsulating spacers 503.

The tri-axial lines 401, 601 are advantageous as the boil off, which isat a temperature between the temperature of the cryogenic liquid and theambient temperature, provides a layer of insulation between the deliveryline 403, 603 and the insulating line 407. This insulation is providedby cold gases, that in prior art systems would have merely been ventedto the atmosphere. As will be appreciated, on start up the cold gasflowing from the probe will help to cool the delivery line 603 ascryogen is supplied. The vacuum in the insulating line 607 will help toensure the insulation.

Further, these tri-axial lines 401, 601 are advantageous, as in order toallow for re-use of a line in surgery it must be sterilisable.Sterilisation is generally accomplished by autoclaving, which consistsessentially of high pressure and temperature steam treatment. Thepresent tri-axial lines 401, 601 mitigate the need to provide aninsulating line capable of maintaining a vacuum after several autoclavecycles.

FIG. 7A shows an alternative line 701 in schematic cross-sectional viewfor use with examples of the present invention. The alternative line 701is a bi-axial line, and comprises a central delivery line 703 and anexhaust line 705. The delivery line 703 is within the exhaust line 705.The exhaust line 705, in use, carries cold boil off away from the probe.Hence, in use, the cold boil off acts to insulate delivery line 703 fromambient temperatures. This reduces undesirable condensation on theoutside of the bi-axial line 701 and evaporation losses from the supplyof cryogen via the delivery line 703. The exhaust line 705 may be of aflexible material, such as silglass, accordingly, spiders 707 or othersuitable spacers may be provided to prevent the exhaust line 705completely collapsing under vacuum, when used with the presentinvention.

FIG. 7B shows an alternative example of line 701′ the supply line 703′can be surrounded by an insulating line 708. A separate exhaust line705′ is provided to take nitrogen gas from the probe tip. In thisexample the insulating line has a vacuum applied thereto. Preferably thevacuum is provided by the vacuum source in communication with theexhaust line 705′.

FIG. 8 shows an alternative delivery line assembly 801 in schematiccross-sectional view for use with the present invention. The deliveryline assembly 801 comprises a delivery line 803, which is insulated bymeans of ceramic collars 805.

The ceramic collars 805 lie adjacent each other and cover substantiallythe whole length of the feed line 803. The ceramic collars 805 have aconcave curved portion 807 at one end and a convex curved portion 809 atthe other end. The concave curved portion 807 of one ceramic collar iscomplementary with a convex curved portion 809 of another, such that thedelivery line 803 may be bent and still substantially insulated by theceramic collars 805.

The ceramic collars 805 may be glazed, such that they are impermeable.Such glazed ceramic collars are more hygienic than unglazed ceramiccollars. The delivery line assembly 801 is durable and can be sterilisedby means of an autoclave, accordingly, such delivery line assemblies 801are advantageous.

Any of the tri-axial line 401, the alternative tri-axial line 601, thealternative bi-axial line 701 or the delivery line assembly 801 may beused with any of the described cryogenic systems.

FIG. 9 shows a further cryogenic system, indicated generally at 901. Thecryogenic system 901 comprises apparatus for supplying liquid cryogen903, an intermediate cryogen storage apparatus 905, a probe 907, and avacuum source 909. The apparatus for supplying liquid cryogen 903 isconnected to the probe via supply line 911, intermediate cryogen storageapparatus 905, and delivery line 913. The probe 907 is also connected tothe vacuum source 909 by means of exhaust line 915.

The apparatus for supplying liquid cryogen 903 (which may be that asdescribed in WO 96/30816 the entire disclosure of which is includedherein by reference) comprises a means for supplying propellant gas, aDewar 917, and a supply pipe 919 which, in use, has an end beneath thesurface of the liquid cryogen. The Dewar 917 may be of any appropriatesize and may be approximately 60 litres. The means for supplying apropellant gas comprises a pressure raising coil 921, an automaticpressure control valve 923, and a pressure control regulator 925. Thepressure raising coil 921 is connected to the automatic pressure controlvalve 923 which is operable to regulate the pressure of the propellantgas by the user. The pressure control valve 925 is connected to thepressure control regulator 925. The pressure control regulator 925 isoperable to maintain a preset propellant gas pressure within the Dewar917 when the pressure control valve 923 is open. The preset propellantgas pressure may be of any appropriate value. e.g. 414 kPa (60 psi). Thepressure control regulator 925 is connected to Dewar 917. In use,propellant gas is fed above the surface of the liquid cryogen containedwithin the Dewar 917. The Dewar 917 is sealable such that, in use, thepressure of the propellant gas may displace liquid cryogen along thesupply pipe 919. The supply pipe 919 has, in use, one end beneath thesurface of the liquid cryogen contained within the Dewar 917 and theother end is connected to the supply line 911.

The apparatus for supplying liquid cryogen 903, also comprises a fillline 927 and fill valve 929 for filling the Dewar 917 with liquidcryogen. The apparatus for supplying liquid cryogen 903 also comprises acontents gauge 931, the contents gauge 931 is a capacitance contentsgauge which displays the remaining contents and communicates this value,for example to a control system. The apparatus 903 further comprises asafety relief valve 933 and a bursting disc 935 to prevent the apparatus903 from reaching an excessive pressure. The apparatus 903 furthercomprises a pressure gauge 937 which displays the system pressure andcommunicates this value, for example to a control system. The apparatus903 also comprises a gas vent 939 to release pressure within theapparatus 903 when desired.

The cryogenic system 901 also comprises an optional intermediate cryogenstorage apparatus 905 which connects the supply line 911 and thedelivery line 913. The purpose of the intermediate cryogen storageapparatus 905 is to provide cryogen at a location nearer to the probe907 than is possible in known prior art systems. Since the Dewar 917 ofthe apparatus for supplying liquid cryogen 903 has a volume ofapproximately 60 litres and a height of approximately 1 meter it isusually not possible for the apparatus for supplying liquid cryogen 903to be in close proximity to the probe 907. The distance between theapparatus for supplying liquid cryogen 903 and the probe is typically 2metres, the intermediate cryogen storage apparatus 905 is typicallyplaced such that the supply line 911 and the delivery line 913 are 1metre in length. However, the most important feature is to shorten thelength of delivery line 913, such that the time from initiating coolingof the probe 907 to the probe 907 actually cooling is minimised.

The intermediate cryogen storage apparatus 905 comprises an intermediateDewar 941. The intermediate Dewar 941 connects the supply line 911 andthe delivery line 913, its purpose is to allow the supply line 911 to becooled to liquid cryogen temperature before the delivery line 913. Thesupply line 911 may be vacuum insulated. Such vacuum insulation, e.g.provided by a permanently vacuum insulated line, further reduces losses,e.g. evaporative losses, of cryogen. The intermediate cryogen storageapparatus 905 includes a vent valve 943, a thermocouple 945, aconnection 947 to the supply line 911 and a connection 949 via thedelivery line 913 to the probe 907. The connection to the delivery line949 must be beneath the surface of the liquid cryogen in use, such thatliquid cryogen is able to pass along the delivery line 913. Thethermocouple 945 and the vent valve 943 must be towards the top of theintermediate Dewar 941, such that the thermocouple 945 can sense whenthe intermediate Dewar 941 is approaching full and the vent valve 943can vent gaseous cryogen and not liquid cryogen. The intermediatecryogen storage apparatus 905 also comprises a safety relief valve 951and a bursting disc 953 to prevent the apparatus 905 from reaching anexcessive pressure.

In use, liquid nitrogen is fed from the apparatus for supplying liquidcryogen 903, by the propellant gas along the supply line 911 tointermediate Dewar 941. Whilst the cryogenic fluid is fed along(initially warm, that is above the boiling point of liquid nitrogen) thesupply line 911 it boils and/or evaporates and the boil off is ventedthrough vent valve 943. Once the intermediate Dewar 941 fills withliquid cryogen, the thermocouple 945 begins to cool. Once apredetermined temperature is reached (approximately the boiling point ofthe liquid cryogen in use) the propellant gas pressure is removed andthe vent valve 943 is closed. In this way the supply line 911 can becooled in advance of initiating a freeze state of the probe 907. Oncethe vent 943 is closed the whole assembly functions as a delivery linein order to allow cryogen flow to the probe 907 valve 961 is openable.

The cryogenic system 901 also comprises means for warming the probe 907as part of a thaw cycle. Connected to the apparatus is a heater 955 forheating nitrogen gas to thaw the probe. The heater 955 is connected tothe delivery line 913 via a valve 957 and a three-way connection 959.There is also provided a valve 961 between the intermediate cryogenstorage apparatus 905 and the three-way connection 959. With thisarrangement by operation of the valves 961, 957 it is possible to supplyeither liquid cryogen or hot nitrogen gas to the probe 907 as desired.By providing appropriate connections to the heater 955 it is possible toflow heated gas in either direction around the apparatus, as may bepreferable.

The probe 907 is connected to a vacuum source 909 by means of exhaustline 915. The vacuum source 909 comprises a vacuum tank 963, a pump 965and a vent 967. The vacuum tank 963 also comprises a heater 969 withinthe base of the tank 963, the purpose of the heater 969 is to boil anyliquid cryogen that may arrive in the vacuum reservoir 963.

Between three-way valve 959 and probe 907 the delivery line 913 and theexhaust line 915 may be adjacent. Accordingly, the lines 913, 915 may beany of the tri-axial line 401, the alternative tri-axial line 601, thealternative line 701 or the delivery line assembly 801.

In use, the probe 105 (or any of 105, 300, 901) is inserted by a surgeon(the user) into a patient such that the region (such as a tumor) to becryo-ablated is adjacent or in contact with the thermally conductingregion of the tip 205. The cryogenic system 101 is activated whendesired by the surgeon which may be before the probe is located in vivo.When the system is activated the valve 123 opens and propellant gaspressure is applied to Dewar 115. In the operating condition Dewar 115is sealed such that the propellant gas acts on the liquid cryogen withinDewar 115. Thus, liquid cryogen is forced along the pipe 117 towardsdelivery line 109. The liquid cryogen as it comes into contact with thewarm (above liquid nitrogen temperature) pipe 117 and feed line 109 willboil and/or evaporate. This liquid cryogen boil-off is removed byapplication of a vacuum to delivery line 109 via probe 105 and exhaustline 111, this vacuum is supplied by vacuum source 107.

As with prior art systems if the tube 117 and delivery line 109 are warm(that is—above the liquid cryogen boiling point) the liquid cryogen onceit enters the feed tube 117 and delivery line 109 will begin to boiland/or evaporate until the feed tube 117 and delivery line 109 aresufficiently cold. However, unlike prior art systems, when liquidnitrogen is fed along feed tube 117 and delivery line 109 the vacuumsource 107 operates to provide a vacuum on exhaust line 111. The vacuumapplied to exhaust line 111 is applied to the delivery line 109 anddelivery tube 117 via the probe 105. Whereas, in prior art devices theboil off from liquid nitrogen coming into contact with warm feed tube117 and delivery line 109 hinders the flow of liquid nitrogen along feedtube 117 and delivery line 109, the present invention literally “sucksoff” the boil off via probe 105 and exhaust line 111. Thus applicationof vacuum overcomes, or at least substantially reduces, the negativeeffects of phasing experienced in prior art devices.

This improves freeze rates and hence times, and provides reducedvariation of pressure and flow in successive uses. Reduced freeze ratesare particularly advantageous, providing shorter operating times, whichmay be critically important for patients undergoing traumatic surgicalprocedures. The present invention may provide a probe which begins tocool after less than 2 minutes from initiation of a freezing cycle.Moreover, in the initial state the application of a vacuum ensures thatair present in the conduits is swiftly drawn through the apparatus,thereby limiting the opportunity for liquefaction of the air orsolidification of any water.

During initial operation (from warm) a large volume of nitrogen boilsoff and a high rate of evacuation is required, initially the systemoperates at a maximum flow of liquid nitrogen until a probe tip thermalcouple 133 reports the maximum for each temperature of −196° C.

However, once the delivery tube 117 and delivery line 109 have beenreduced to working temperature the rate of liquid nitrogen supply andevacuation can be reduced.

Once the feed line 109 has cooled sufficiently along its length liquidcryogen arrives at the probe 105. The liquid cryogen arrives at inlet209 and is fed along feed tube 212 from the proximal end of the probe201 to the distal end of the probe 203. Thus the liquid cryogen arriveswithin the tip 205 of the probe 105. Here the liquid cryogen comes intocontact with a dispersive medium such as a sintered bronze region 215 ofthe probe tip 205. The sintered bronze region 215 promotes boilingand/or evaporation by provision of nucleation sites. Once the liquidcryogen has boiled and/or evaporated it is removed via exhaust tube 217,exhaust port 211, exhaust line 111 and vacuum source 107. The boilingand/or evaporation of liquid cryogen in sintered bronze region 215within the probe tip 205 cools the probe tip 205 to cryogenictemperatures.

The probe tip 205 which is thermally conducting is thus able to coolsurrounding tissue. This freezes the water in surrounding tissue andforms an ice ball 221. Cooling cells below −20° C. is known to killthem.

Several factors determine the size of the ice ball formed. These factorsinclude both the temperature of the probe tip and the capacity of theprobe 105 to remove heat from surrounding tissue. Thus, the sinteredbronze region 215 is particularly advantageous as it promotes boilingand/or evaporation removing the latent heat of evaporation from theprobe tip 205 and surrounding tissue, forming ice ball 221.

The flow rate of liquid cryogen is controlled by the pressure ofpropellant gas acting on the liquid cryogen within Dewar 115 and thevacuum applied by vacuum source 107. The vacuum supplied by vacuumsource 107 is controlled by valve 129, the pump 127 operatingintermittently to provide a predetermined vacuum level within vacuumreservoir 125. Preferably, significant quantities of liquid cryogen boilwithin sintered bronze region 215. That is—the flow rates are adjustedto favour boiling within region 215.

For example, if the probe 105 has and outer diameter of 5 mm and aninner diameter of 2 mm, once the probe is fully cooled the flow ratewill be approximate between 5 and 6 litres per minute.

When the cryogenic system 101 is operating at its most efficient levelall, or at least substantially all, of the liquid cryogen boils withinthe probe tip 205. Thus appropriate control of cryogen supply and vacuumapplication reduce wastage and ensure that the apparatus functionsoptimally.

During operation of the system 101 the size of the ice ball 221 grows.Once an ice ball 221 of a desired size is formed, the surgeon switchesthe system to thaw mode. In thaw mode, nitrogen gas is fed from nitrogengas cylinder 119 to the heater which heats the nitrogen gas. The hotnitrogen gas is then fed along delivery line 109 to probe 105. The hotnitrogen gas displaces any liquid nitrogen remaining within the deliveryline 109, probe 105 and exhaust line 111. Further, the hot nitrogen gasheats the probe tip 205. The sintered bronze region 215 having a largesurface area readily absorbs heat from the nitrogen gas. Once the probetip has thawed sufficiently it can be removed from the patient by thesurgeon. The use of nitrogen as a purge gas (as opposed to, say, air) ispreferably since it will only form nitrogen condensate (as opposed towater or other impure condensate).

Alternatively, the system 101 may be arranged and operated such that thehot purge gas flows in a reverse direction along exhaust line 111,through probe 105 and out of inlet line 109.

The system may also provide an auto clean function, which operates byventing high-pressure gas through the probe 105 in a reverse direction,along exhaust line 111 through probe 105 and exiting through deliveryline 109 to remove obstructions in the lines and/or probe.

The components of the system may be controlled from a common controlpanel providing adjustability of flow according to surgical requirementsand so on. The parameters may be controlled according to a set programaccording to surgical requirements.

The cryogenic system 901 is operates in a like manner to the cryogenicsystem 101.

FIG. 10 shows a further example of a probe 140. The probe 140 is similarto that described and shown in FIG. 2 and equivalent reference numeralshave been used. Only the differences will be described. The deliverytube 212 extends along the length of the probe 140, through a mountingspacer 141 and into the dispersive medium 215. As shown in FIG. 10a ,the mounting spacer 141 comprises a central aperture 142 for mountingthe delivery tube as well as enabling the delivery tube to passtherethrough into the dispersive medium. The dispersive medium acts as aporous delivery face for the cryogenic liquid. The mounting spacer 141also comprises a plurality of further apertures 143 to allow egress offluid, such as cryogenic gas generated from the cryogenic liquidboiling/evaporating when coming into contact with the dispersive medium.The cryogenic gas is then able to be drawn out from within the probebody though exhaust line 217, which is in fluid communication with avacuum source (not shown).

As shown in FIG. 10b , the probe tip 205 comprises an outersurface/housing 251 of a thermally conductive material, for examplesilver, which covers and hermetically seals the dispersive medium 215within the probe. The sintered material is provided with a cavity 252 toreceive an end of the delivery tube 212. The use of a sintered metal,such as copper or brass, as the dispersive medium provides thermalproperties and a thermal conductivity which are advantageous in theexchange of heat between the cryogen, the dispersive medium and theouter surface of the probe tip.

In use, a cryogenic liquid is delivered through the delivery tube to thedispersive medium and boils/evaporates at nucleation sites therein. Theresultant cryogenic gas is then expelled from the probe via the exhausttube and drawn away by a vacuum from a vacuum source located on theexhaust side of the system. However, not only can the vacuum source beused simply to draw the cryogenic gas away from the dispersive mediumand out of the probe, but also, in certain examples of the invention,the cryogenic system is configured such that the cryogenic liquid iscaused to be drawn through the delivery tube to the dispersive mediumdue to action caused by a vacuum applied via the exhaust tube from avacuum source (“negative pressure”) located on the exhaust side of thesystem. Such a “pulling” of the cryogenic liquid from the exhaust sideis to be contrasted to previous cryogenic systems wherein the cryogenicliquid is “pushed” from the delivery side (i.e. wherein the cryogenicliquid is forced through the delivery tube to the dispersive medium by apressure source/pump (“positive pressure”) located on the delivery sideof the system).

The use of a sintered material as the dispersive medium advantageouslyenable a control and/or configuration of the material's porosityproperties. The porous nature of sintered material and its use inexamples of the present invention enables the cryogenic gas to freelypass through and egress from the dispersive medium. This enables anegative pressure from the vacuum source to be communicated through: theexhaust line, the dispersive medium and the delivery line to thecryogenic liquid source, i.e. the vacuum source can be in fluidcommunication with the source of the cryogenic liquid. The vacuum'snegative pressure, duly communicated to the cryogenic liquid, provides alifting effect/pulling or ‘sucking’ of the cryogenic liquid towards theprobe tip and to the dispersive medium therein.

As a result of the thermal transfer that occurs between the cryogenicliquid, dispersive medium and probe tip during use, an ice ball 221 canform around the probe tip 205. When the probe tip is inserted intotissue required for destruction an ice ball within the surroundingtissue is formed reducing the tissue in the ice ball below its survivaltemperature (−20° C.).

The centre of the ice ball 214′ is typically as cold as the thermalsource generating the ice ball. Where, for example, liquid Nitrogen isused as the cryogenic liquid, tissue immediately adjacent to the probetip will be reduced to −196° C. or thereabouts. The margins of the iceball 221′ will be at 0° C. Between these two points 214′ 221′ there is athermocline and depending on how long and how quick the freeze takesplace will determine how much of the ice formed is effectively lethal tothe frozen tissue.

The above cryogenic systems and their methods of use provide:

-   -   Improved freeze rates    -   Reduced losses    -   Shorter freeze times, particularly, the probe may begin to cool        in less than 2 minutes    -   Reduced variation of pressure/flow on cryoprobe performance    -   Increased safety    -   The capacity to allow for multiuse of probes and other        components

Each of the probes describe above may be used with the system set out inFIG. 9, providing appropriate couplings are provided.

FIG. 11A illustrates a flow path of cryogen through an apparatus forcryosurgery 1101 during a freeze mode of operation. In the freeze mode,liquid cryogen is drawn from storage Dewar 103 to the tip of probe 105via vacuum pump 107. The liquid cryogen evaporates in the sinteredmaterial of the probe tip. The gaseous cryogen is exhausted from theprobe via the vacuum pump 107 and vented out to atmosphere.

FIG. 11B shows the apparatus 1101 during a thaw mode of operation, forexample after a freezing mode had taken place.

The apparatus for cryosurgery 1101 comprises a flash chamber 1102. Thisis a pressure vessel manufactured from thick walled aluminium tubesealed at both ends and fitted with two metric threaded ports. A pipe1103 submerged in the liquid nitrogen of the cryogen source 103 isconnected to one of the ports on the flash chamber. The second port isconnected to the vacuum pump 107 via a valve 1104. There is a checkvalve 1105 positioned between the connection to the flash chamber andthe pipe submerged in the liquid nitrogen.

When the valve 1104 opens suction is applied to the flash chamber. Oncethe air is evacuated, the check valve 1105 opens and a small quantity ofliquid nitrogen is drawn from the Dewar into the flash chamber. When theliquid arrives in the flash chamber it immediately evaporates when itcontacts the heated walls of the flash chamber.

Because a volume of liquid nitrogen expands into a volume of nitrogengas at the ratio of 700 to 1, the flash chamber quickly fills withnitrogen gas under pressure. This pressure forces the check valve toclose and the flow of liquid nitrogen into the flash chamber is turnedoff. The pure nitrogen gas then flows from the flash chamber via thecontrol valve 1104 through a heater/heat exchanger 1106 and to the probe105 where the heat from the gas is transferred to the probe tip so thatthawing of the probe tip may take place. The flash chamber thus acts asa source of gaseous cryogen for delivery to the probe.

The gas from the probe is then re-circulated via the vacuumsource/compressor 107 back into the heater/heat exchanger 1106 and againback into the probe 105. This loop continues until the thaw is completeat which time the valve 1104 closes and suction is no longer applied tothe flash chamber at which point it remains pressurised until requiredagain.

A valve 1106 in the exhaust line and the vacuum pump 107 allows, duringa freezing mode, the spent nitrogen gas generated during a freeze cycleto pass to the atmosphere. The valve also allows, during a thawing mode,nitrogen gas to be re-circulated around the probe and heated beforebeing passed through the probe in a thaw cycle.

Re-using the cryogenic gas in this manner avoids the need to useair/atmospheric gas as the thawing medium. If air/atmospheric gas wereto be used, moisture would need to be eliminated from the air using acombination of desiccant filters/compressed air dryers and processheaters to eliminate the moisture. If moisture were to reach the probetip and subsequently remained there whilst a freeze cycle was in placethis would cause a blockage in the probe. Accordingly, reliability ofthe apparatus is improved since there is no reliance on a user toremember to change the desiccant filter and carry out routinemaintenance on a compressed air dryer. Therefore a simpler and morereliable method is provided.

Also, re-using the cryogenic gas in this manner avoids the need to use aseparate source of thawing medium. The apparatus 1101 effectively,efficiently and cheaply enables access to the enormous volumes ofgaseous cryogen available in liquid form inside the Dewar cryogensource.

It will be appreciated that the invention is not limited to the forgoingdescription of a preferred example and that modifications may be madewithin the scope of the Claims appended hereto. Indeed, variousmodification will be apparent to those skilled in the art, for example,the microprocessor control could be replaced by direct control be askilled technician. Instead of liquid nitrogen an alternative liquidcryogen may be used. An alternative method of supplying liquid cryogen.e.g. a pump, may be used. The probe tip may be warmed by use of anelectric resistance coil instead of hot nitrogen gas. Any controllablevacuum source may be used with the present invention.

1. A method for effecting cryosurgery on soft tissue tumours, the methodcomprising providing an apparatus comprising a cryogen source, adelivery tube, a probe, and a vacuum source; locating the probe on or ina target area of soft tissue tumour; and drawing cryogen from thecryogen source along the delivery tube to the probe using the vacuumsource.
 2. The method according to claim 1, comprising boiling orevaporating the cryogen within the probe.
 3. The method according toclaim 1, comprising dispersing the cryogen through a dispersive mediumin the probe.
 4. The method according to claim 3, comprising dispersingthe cryogen through a porous material and/or a sintered material.
 5. Themethod according to claim 1, wherein the probe further comprises athermally conductive tip, the method comprising locating the thermallyconductive probe tip on or in the target area of soft tissue tumour toeffect cryosurgery.
 6. The method according to claim 1, comprisingforming an ice ball on or in the target area of soft tissue tumour. 7.The method according to claim 1, comprising exposing the target area ofsoft tissue tumour to a temperature of −20° C. or below.
 8. The methodaccording to claim 1, wherein the probe comprises a concentricperipheral insulating conduit, the method further comprisingcontinuously evacuating the insulating conduit using the vacuum source.9. The method according to claim 1, wherein the apparatus furthercomprises an exhaust tube, the method further comprising drawing cryogenfrom the cryogen source along the delivery tube, to the probe, and alongthe exhaust tube using the vacuum source.
 10. The method according toclaim 1, further comprising recirculating the cryogen received from theprobe to the delivery tube for reuse.
 11. The method according to claim1, comprising drawing the cryogen from a primary cryogen source to asecondary cryogen source, along the delivery tube, to the probe usingthe vacuum source.
 12. The method according to claim 11, comprisingdrawing the cryogen from the primary cryogen source to the secondarycryogen source prior to locating the probe on the target area of softtissue tumour.
 13. The method according to claim 1, wherein the cryogencomprises liquid cryogen, the method comprising drawing liquid cryogenfrom the cryogen source along the delivery tube to the probe using thevacuum source.
 14. The method according to claim 13, further comprisingdrawing liquid cryogen from the cryogen source along the delivery tubeto the probe at a rate of 5 to 6 litres per minute.
 15. The methodaccording to claim 1, comprising heating the cryogen for delivery to theprobe.
 16. The method according to claim 1, wherein a source of positivepressure is not provided or required to push cryogen from the cryogensource to the probe.
 17. A method of generating an ice ball within asoft tissue tumour, the method comprising providing an apparatuscomprising a cryogen source, a probe comprising a thermally conductivetip; locating the thermally conductive tip of the probe in or on atarget area of soft tissue tumour and drawing cryogen from the cryogensource to the probe under the influence of negative pressure so as togenerate an ice ball about the periphery of the thermally conductivetip.
 18. The method according to claim 17, comprising generating an iceball with a temperature between −20° C. and −196° C.
 19. The methodaccording to claim 17, comprising dispersing the cryogen through adispersive medium in the thermally conductive probe tip.
 20. The methodaccording to claim 17, comprising warming the thermally conductive tipafter generation of the ice ball to thaw the ice ball by deliveringheated gas to the probe.